Natural selection and infectious disease resistance in humans

Dangerous pathogens are among the strongest forces shaping recent human evolution. One such pathogen is Vibrio cholerae, the bacteria that causes cholera, an ancient and deadly disease. Working with researchers from iccdr,b in Bangladesh, MGH and Harvard University, we have shown that we can use the marks left by ancient selection to identify host genetic variants associated with cholera susceptibility. We are now integrating signals of natural selection with genomewide association and functional data to identify new host immune factors likely influencing cholera resistance. We propose to use this approach to investigate other historically prevalent infectious diseases, such as viral hemorrhagic fevers and hepatitis, as well as common, polygenic diseases, such as inflammatory bowel disease, for which the associated genes may have been historically selected.

Artificial selection and behavioral genetics in dogs

For thousands of years, humans have bred dogs to excel at behaviors like herding, tracking and retrieving. Our work on obsessive compulsive disorder in dogs and in humans demonstrated that dogs are an excellent model for human psychiatric diseases. We are now expanding this research to a broader spectrum of canine behaviors and more genetically diverse group of dogs. Using new high, throughput genomic technologies, we aim identify the neurological pathways that underlie behaviors favored by our ancient ancestors, and understand how these genetic changes led to changes in behavior.